Implementation of a human hepatocyte culture system to study the liver stages of the malaria parasites

• Grant number: 23/08379-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2024
• Status: Discontinued
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Carsten Wrenger
• Grantee: André Filipe Rivais Martins Barateiro
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/14768-2 - "Hit-to-lead" approach for the rational design of compounds against P. vivax hypnozoites, BE.EP.PD

Abstract

Malaria still represents a significant public health problem worldwide, yet it affects disproportionally people leaving in impoverished and developing countries, killing more than half a million individuals year-round. So far, we are unlikely to meet the ambitious goal of significantly reducing malaria incidence and mortality by 90% until 2030, mostly due to vector-parasite adaptation, demographic, climatic and ecologic events and, more recently, the COVID-19 pandemic. The scientific community set an optimistic deadline for eradication in 2050, which can only be achieve with the engagement of international stakeholders and policy makers, who were asked to reinforce public health measures and invest in R&D initiatives with the potential to transform and generate new tools to fight malaria. In this context, and since regional elimination is key for global eradication, local stakeholders in endemic countries should invest in R&D initiatives that can generate innovative tools to solve context-specific malaria-related problems. In Brazil, malaria has specific epidemiological and clinical features such as the ongoing transmission of both P. falciparum and P. vivax, the emergence of drug-resistant strains, and relapsing malaria, which is affecting the elimination agenda. These particular challenges can only be addressed with relevant research models used to produce vaccines to pre-erythrocytic stages, diagnostics for asymptomatic parasite carriers, and safe anti-relapse drugs. Herein, I propose to take advantage of the Brazilian research landscape to implement a self-assembly co-culture system of primary human hepatocytes with supportive non-parenchymal cells that can be used to develop new therapeutics and study the most diverse biological aspects of the malaria parasites' liver stages.